Sex steroidal regulation of uterine leiomyoma growth and apoptosis

被引:217
作者
Maruo, T [1 ]
Ohara, N [1 ]
Wang, J [1 ]
Matsuo, H [1 ]
机构
[1] Kobe Univ, Grad Sch Med, Dept Obstet & Gynecol, Chuo Ku, Kobe, Hyogo 6500017, Japan
关键词
apoptosis; GnRH agonist; growth factor; leiomyoma; sex steroid hormone;
D O I
10.1093/humupd/dmh019
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Uterine leiomyomas develop during the reproductive years and regress after menopause, indicating ovarian steroid-dependent growth potential. Although the clinical and biochemical observations have traditionally supported an important role for estrogen in the promotion of leiomyoma growth, there is also increasing evidence to suggest the involvement of progesterone in the pathogenesis of leiomyoma. In this review, much attention has been paid to characterizing the molecular mechanisms of sex steroidal regulation of leiomyoma growth and apoptosis by evaluating the effects of sex steroids on the expression of growth factors and apoptosis-related factors. The effects of GnRH agonist on the expression of these factors in leiomyoma are also described. 17beta-Estradiol up-regulates epidermal growth factor (EGF) receptor, but down-regulates p53 protein in leiomyoma cells, whereas progesterone augments EGF and Bcl-2 protein, but inhibits insulin-like growth factor (IGF-I) and tumour necrosis factor (TNFalpha). Since it is now evident that EGF and IGF-I act as local factors which stimulate leiomyoma growth, these findings suggest that progesterone may have dual actions, stimulatory and inhibitory, on leiomyoma cell growth and survival, depending on the local growth factor conditions around each leiomyoma. This may explain why the size of uterine leiomyomas during the use of levonorgestrel-releasing intrauterine system (LNG-IUS) increases in some but decreases in other instances. This may also explain why the size of leiomyomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones. Moreover, there is further evidence to suggest that the interactions between estrogen receptors and progesterone receptors may be involved in the modulation of gene transcription activity in leiomyoma. This review demonstrates that leiomyoma growth is integrally regulated by the complex cross-talk between sex steroid hormones and growth factors.
引用
收藏
页码:207 / 220
页数:14
相关论文
共 182 条
  • [1] Sex steroid regulation of insulin-like growth factor system gene expression and proliferation in primate myometrium
    Adesanya, OO
    Zhou, J
    Bondy, CA
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (05) : 1967 - 1974
  • [2] Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding
    Anania, CA
    Stewart, EA
    Quade, BJ
    Hill, JA
    Nowak, RA
    [J]. MOLECULAR HUMAN REPRODUCTION, 1997, 3 (08) : 685 - 691
  • [3] LEIOMYOMA PRIMARY CULTURES HAVE ELEVATED TRANSCRIPTIONAL RESPONSE TO ESTROGEN COMPARED WITH AUTOLOGOUS MYOMETRIAL CULTURES
    ANDERSEN, J
    DYREYES, VM
    BARBIERI, RL
    COACHMAN, DM
    MIKSICEK, RJ
    [J]. JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION, 1995, 2 (03) : 542 - 551
  • [4] Transforming growth factor-β3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation
    Arici, A
    Sozen, I
    [J]. FERTILITY AND STERILITY, 2000, 73 (05) : 1006 - 1011
  • [5] Expression, menstrual cycle-dependent activation, and bimodal mitogenic effect of transforming growth factor-β1 in human myometrium and leiomyoma
    Arici, A
    Sozen, I
    [J]. AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2003, 188 (01) : 76 - 83
  • [6] Barbarisi A, 2001, J CELL PHYSIOL, V186, P414, DOI 10.1002/1097-4652(2000)9999:999<000::AID-JCP1040>3.0.CO
  • [7] 2-E
  • [8] TGF-BETA INDUCES BIMODAL PROLIFERATION OF CONNECTIVE-TISSUE CELLS VIA COMPLEX CONTROL OF AN AUTOCRINE PDGF LOOP
    BATTEGAY, EJ
    RAINES, EW
    SEIFERT, RA
    BOWENPOPE, DF
    ROSS, R
    [J]. CELL, 1990, 63 (03) : 515 - 524
  • [9] GROWTH REGULATORY PROPERTIES OF ENDOTHELINS
    BATTISTINI, B
    CHAILLER, P
    DORLEANSJUSTE, P
    BRIERE, N
    SIROIS, P
    [J]. PEPTIDES, 1993, 14 (02) : 385 - 399
  • [10] Estrogen receptors (ERα/ERβ) in normal and pathological growth of the human myometrium:: pregnancy and leiomyoma
    Benassayag, C
    Leroy, MJ
    Rigourd, V
    Robert, B
    Honoré, JC
    Mignot, TM
    Vacher-Lavenu, MC
    Chapron, C
    Ferré, F
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1999, 276 (06): : E1112 - E1118